Current evidence indicates that circulating immune complexes (CIC) may be a major agent for chronic tissue damage in a number of diseases, including collagen-vascular, autoimmune, neoplastic and infectious diseases. We have recently found that CIC are found in about 60% of patients with selective IgA deficiency, and preliminary studies indicate that dietary bovine proteins, largely derived from milk, may be involved as antigens in as much as 80% of CIC found in individuals who lack IgA. The development of an in vivo milk ingestion test has made possible direct kinetic studies of immune complex formation under standardized conditions. We now propose to investigate this immune complex in vivo and in vitro: 1) the kinetics of formation and dissolution; 2) the molecular nature of the complexes and the identity of the incorporated antigens; 3) the effect produced by the rapid appearance of CIC upon the components of the complement cascade; and 4) the relationship between this phenomenon and: 1) the possible development of coexistence of autoimmune abnormalities, 2) the spectrum to immunologic capabilities, and 3) the clinical course of the patients in whom it is observed. Since experimental immune complex disease in animals is primarily a manifestation of arterial injury, we shall be particularly interested in the development of renal and vascular problems in this group of patients. Selective IgA deficiency is probably one of the commonest of immunologic disorders. Since CIC are currently believed to be a major agent of tissue and arterial injury in a number of pathologic states, it will be of great importance to understand the molecular charateristics and natural history of the CIC found in IgA deficiency and to relate the presence of complexes to the possible development of chronic disease.